Cefoperazone
Cefoperazone: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Drug interactions
- 14. Analogs
- 15. Terms and conditions of storage
- 16. Terms of dispensing from pharmacies
- 17. Reviews
- 18. Price in pharmacies
Latin name: Cefoperazone
ATX code: J01DD12
Active ingredient: cefoperazone (cefoperazone)
Producer: JSC "Biosintez" (Russia), Pharmaceutical company LEKKO (Russia), KRASFARMA (Russia), DEKO Company, LLC (Russia), RUE "Borisov plant of medical preparations" (Belarus)
Description and photo update: 2018-09-07
Cefoperazone is a broad-spectrum antibacterial drug.
Release form and composition
The dosage form of Cefoperazone is a powder for the preparation of a solution for intravenous (iv) and intramuscular (i / m) administration: from white to white with a yellowish tinge, hygroscopic (in a glass bottle 500, 1000 or 2000 mg, in a cardboard box 1, 10, 25, 50 vials).
Composition of 1 mg powder: active substance - cefoperazone (in the form of sodium cefoperazone), in an amount of 1 mg.
Pharmacological properties
Pharmacodynamics
Cefoperazone is a third-generation semi-synthetic cephalosporin antibiotic with a broad spectrum of activity. The mechanism of bactericidal action consists in inhibiting the synthesis of cell walls of microorganisms by acetylation of membrane-bound transpeptidases and thus disrupting the cross-linking of peptidoglycans, which is necessary for the strength and rigidity of the cell wall. Cefoperazone sodium has in vitro activity against a wide variety of clinically significant microorganisms, but is resistant to most beta-lactamases.
Cefoperazone is active against the following gram-positive microorganisms: Staphylococcus epidermidis, Staphylococcus aureus (strains producing and non-producing penicillinase), Streptococcus pyogenes (beta-hemolytic streptococcus group A), Streptococcus faccus pneumoniae agal.
Gram-negative organisms susceptible to the action of cefoperazone: Klebsiella spp. (including Klebsiella pneumoniae), Escherichia coli, Citrobacter spp., Enterobacter spp., Proteus vulgaris, Proteus mirabilis, Haemophilus influenza, Providencia spp. (including Providencia rettgeri), Morganella morganii, Shigella spp., Salmonella spp., Serratia spp. (including Serratia marcescens), Pseudomonas spp. (including Pseudomonas aeruginosa), Neisseria gonorrhoeae (beta-lactamase producing and non-producing strains), some strains of Acinetobacter spp., Yersinia enterocolitica, Bordetella pertussis, Neisseria meningitidis.
Anaerobic microorganisms sensitive to cefoperazone: gram-positive cocci (including Peptostreptococcus spp., Peptococcus spp.), Gram-positive spore and non-spore-forming anaerobes (Eubacterium spp., Clostridium spp., Lactobacillus fragilus spp., Fusobacterium spp. And other strains of Bacteroides spp.).
Pharmacokinetics
After i / m administration of 250 and 500 mg of cefoperazone, C max (maximum concentration) in the blood serum is 22 and 33 μg / ml, respectively. The time to reach C max after i / m injection is 1–2 hours, after i / v injection - at the end of the infusion. From 82 to 93% of the active substance binds to blood plasma proteins.
Cefoperazone reaches therapeutic concentrations in tissues and body fluids: synovial, peritoneal, ascitic fluids, bile, urine, gallbladder walls, sputum, lungs, sinus mucosa, palatine tonsils, kidneys, atria, ureters, testes, prostate gland, fallopian tubes, uterus, umbilical cord blood, amniotic fluid, bones, as well as in cerebrospinal fluid (with meningitis). Small concentrations of cefoperazone can be found in breast milk.
The volume of distribution (V d) of the substance is in the range from 0.14 to 2 l / kg.
T 1/2 (half-life) averages 2 hours (1.6-2.4 hours) regardless of the route of administration, in newborns and children from 2 months to 11 years - 2.2 hours. T 1/2 with hemodialysis - from 2.8 to 4.2 hours. Cefoperazone is practically not metabolized (less than 1%). It is excreted in active form: 70–80% - with bile, 20–30% - with urine unchanged. In case of impaired liver function and obstruction of the biliary tract, T 1/2 varies from 3 to 7 hours, more than 90% of the dose is excreted by the kidneys.
Therapeutic concentrations in bile are achieved even with severe liver damage, and T 1/2 in such cases lengthens only 2–4 times.
Cefoperazone may accumulate in patients with impaired renal and / or hepatic function.
Indications for use
According to the instructions, Cefoperazone is indicated for use in infectious and inflammatory diseases caused by microorganisms sensitive to cefoperazone:
- bacterial infections of the upper and lower respiratory tract;
- infections of the skin and soft tissues;
- abdominal infections (including cholecystitis, peritonitis, cholangitis and others);
- infectious diseases of the genitourinary system (including gonorrhea);
- sepsis;
- joint and bone infections;
- meningitis;
- infectious and inflammatory diseases of the pelvic organs (endometritis).
In addition, Cefoperazone is used to prevent infectious complications in traumatological, gynecological and abdominal surgical interventions, as well as in cardiovascular surgery.
Contraindications
Contraindication to the use of Cefoperazone is an increased individual sensitivity to cephalosporin and other β-lactam antibiotics, lactation period.
The drug should be used with caution in case of impaired renal and / or liver function, a history of colitis, as well as during pregnancy and in children under 1 year of age.
Instructions for the use of Cefoperazone: method and dosage
Cefoperazone solution is administered intramuscularly or intravenously (drip or slow jet). An intramuscular injection is made deep into a large muscle (gluteus maximus or anterior thigh). Duration of intravenous drip injection - 10-30 minutes or more, depending on the volume of the solution, intravenous jet injection - at least 3-5 minutes.
To prepare a solution intended for intramuscular administration, you can use sterile water for injection or isotonic sodium chloride solution. If it is necessary to prepare a solution with a concentration of 250 mg / ml, to dilute 500 mg of the drug, use 2 ml of solvent, 1000 mg - 4 ml of solvent. In order to reduce pain during intramuscular injections in cases of administration of a solution with a concentration of 250 mg / ml or more, it is recommended to use a solution of lidocaine hydrochloride as a solvent (if the patient does not have a hypersensitivity reaction to lidocaine). For this, a 2% solution of lidocaine is diluted in sterile water for injection. A two-stage dilution method is recommended: first add the required amount of sterile water for injection into the vial and shake until the contents are completely dissolved,then add the required amount of 2% lidocaine solution and mix. The approximate concentration of lidocaine hydrochloride in such a solution is 0.5%.
The sequence of preparation of a solution for intramuscular injection with the required concentration in a vial with 1000 mg of cefoperazone:
- concentration 250 mg / ml: the first stage is the addition of 2.6 ml of sterile water for injection, the second stage is the addition of 0.9 ml of 2% lidocaine;
- concentration 333 mg / ml: the first stage is the addition of 1.8 ml of sterile water, the second stage is the addition of 0.6 ml of 2% lidocaine.
The solution for intravenous administration is prepared extemporaneously. Cefoperazone can be diluted with 5% glucose solution, isotonic 0.9% sodium chloride solution or sterile water for injection.
To prepare a solution for intravenous jet injection, you need to dilute 1000 mg of cefoperazone in 10 ml of a compatible solvent. The maximum dose for intravenous jet administration is: for adults - 2000 mg, for children - 50 mg / kg of body weight.
To prepare a solution for intravenous drip injection, 1000 mg of the drug is diluted in 5 ml of sterile water for injection and the resulting solution is added to the infusion solution (isotonic sodium chloride solution, 5% glucose solution, Ringer's lactate solution) to a concentration of 20 to 100 mg / ml.
Freshly prepared solutions of cefoperazone should be stored at a temperature of 5 to 25 ° C for no more than 24 hours.
Use in adult patients
Doses and duration of drug therapy are set individually, taking into account the nature and severity of the infection.
The recommended average daily dose of cefoperazone in adults is from 2000 to 4000 mg, the drug should be injected every 12 hours in equal parts.
In severe infectious lesions, the daily dose can be increased to 8000 mg, which should also be administered every 12 hours in equal parts.
Cefoperazone therapy can be started pending the results of the sensitivity of microorganisms. In the experiments conducted, when the drug was administered in a daily dose of 12,000 (and even 16,000) mg in equal doses every 8 hours, no complications were found.
In the case of uncomplicated gonococcal urethritis, a single intramuscular administration of cefoperazone at a dose of 500 mg is recommended.
For the prevention of postoperative infectious complications - in / in the introduction of 1000 or 2000 mg 0.5-1.5 hours before the operation. The dose can be repeated every 12 hours, but for no more than 24 hours in most cases.
In surgical interventions with a high risk of infection (for example, in colorectal surgery) or in cases of special risk of infection that has arisen (for example, with joint prosthetics or open heart surgery), the use of Cefoperazone for prophylactic purposes can continue for three days after the completion of the operation.
Patients with impaired renal function are recommended the usual daily dose of 2000-4000 mg. At a glomerular filtration rate of less than 18 ml / min or a serum creatinine level of more than 3.5 mg / dL, the daily dose should not be more than 4000 mg.
In patients with severely impaired liver function, severe obstruction of the bile ducts, cefoperazone should not be used at a dose of more than 2000 mg per day.
In renal and hepatic insufficiency, it is necessary to control the content of cefoperazone in the blood and, if necessary, adjust its dose.
Application in children
Doses and duration of treatment in children are set individually, taking into account the nature and severity of the infectious disease.
The recommended daily dose of cefoperazone in children is from 50 to 200 mg / kg of body weight, the drug should be administered in two doses in equal parts every 12 hours or more, if necessary. The maximum daily dose is 12,000 mg.
The maximum single dose for intravenous administration is 50 mg / kg, the duration of administration should not be less than 3-5 minutes. For newborns (less than 8 days old), it is recommended to inject 50 to 200 mg / kg of body weight per day every 12 hours in equal parts.
The use of daily doses of cefoperazone up to 300 mg / kg in infants and children with severe infectious diseases (including bacterial meningitis) did not cause complications.
Side effects
Possible side reactions from systems and organs:
- digestive system: nausea, vomiting, diarrhea, pseudomembranous colitis, transient increase in aminotransferase and alkaline phosphatase activity;
- hematopoietic organs: bleeding, reversible neutropenia (with prolonged use), anemia;
- allergic reactions: pruritus, urticaria, drug fever, maculopapular rash, eosinophilia, Stevens-Johnson syndrome (malignant exudative erythema), anaphylactoid reactions (including shock). The likelihood of allergic reactions is increased in patients with a history of allergies (especially to penicillin);
- laboratory indicators: an increase in prothrombin time, hypoprothrombinemia, an increase in the enzymatic activity of hepatic transaminases and alkaline phosphatase, a direct false-positive Coombs' test, a decrease in hemoglobin or hematocrit, transient eosinophilia, transient hypercreatinemia;
- local reactions: soreness at the injection site (after i / m injection), phlebitis (after i / v injection);
- others: candidiasis.
Overdose
In case of an overdose of cefoperazone, neurological disorders are possible, including seizures and epileptic seizures.
In such cases, sedative therapy with diazepam is recommended, symptomatic treatment is carried out. The use of hemodialysis is effective.
special instructions
Cefoperazone can be used in combination therapy in combination with other antibacterial drugs.
Before using the drug, it is necessary to find out the patient's allergic history to determine hypersensitivity to cephalosporin antibiotics, penicillins and other drugs.
In case of an allergic reaction during the period of treatment with Cefoperazone, the administration of the drug should be discontinued and appropriate therapy carried out.
In the case of prolonged drug therapy, it is recommended to periodically monitor the functioning of the hematopoietic organs, kidneys and liver. This is especially important for newborn babies, including premature babies.
If it is necessary to use a cephalosporin antibiotic in newborns, including premature babies, it is necessary to take into account the ratio of the expected positive effects of therapy with the probable risk associated with treatment. In newborns with nuclear jaundice, cefoperazone does not displace bilirubin from plasma protein binding sites.
Cefoperazone may cause vitamin K deficiency in some patients, associated with suppression of the intestinal flora that promotes the synthesis of this vitamin. Patients who follow an inadequate diet or who are on parenteral nutrition for a long time, as well as patients with malabsorption syndrome (for example, with cystic fibrosis), are at a higher risk. In such cases, during treatment, prothrombin time control is required and, if necessary, the appointment of vitamin K.
During the period of drug treatment and within five days after its completion, it is recommended to refrain from taking ethyl alcohol due to the possible development of disulfiram-like reactions.
Treatment with antibacterial drugs, including cefoperazone, leads to disturbances in the normal microflora of the colon, as a result of which there is an increased growth of Clostridium difficile bacteria, the formation of toxins A and B and the development of Clostridium difficile-associated diarrhea, which can manifest itself from mild forms of diarrhea to severe forms of colitis fatal. Hypertoxin-producing strains of Clostridium difficile can be resistant to antibiotic therapy, therefore, contribute to an increase in morbidity and mortality. In each case, the development of diarrhea in a patient during treatment with antibacterial drugs should be considered as suspicious for the occurrence of Clostridium difficile-associated diarrhea.
During the period of treatment with cefoperazone, when performing tests using Fehling's or Benedict's solutions, a false positive reaction to urinary glucose is likely.
Influence on the ability to drive vehicles and complex mechanisms
During therapy with Cefoperazone, care should be taken when driving vehicles and performing all types of activities that require a quick motor / mental response and high concentration of attention.
Application during pregnancy and lactation
Cefoperazone can be used in pregnant women when the intended benefit to the mother outweighs the potential risks to the fetus.
If necessary, the use of the drug in women during lactation is recommended to stop breastfeeding.
Pediatric use
Appointment of Cefoperazone to children under 1 year of age requires caution.
With impaired renal function
The use of the drug in patients with renal insufficiency requires monitoring the concentration of cefoperazone in the blood and adjusting its dose if necessary.
If the serum creatinine concentration is above 3.5 mg / dl or the glomerular filtration rate is below 18 ml / min, the dose of the drug should not exceed 4000 mg per day.
For hemodialysis, Cefoperazone should be administered after the end of the dialysis procedure.
For violations of liver function
The drug should be used with caution in case of liver dysfunction.
In patients with severe hepatic impairment, severe obstruction of the bile ducts, it is not recommended to administer cefoperazone at a dose of more than 2000 mg per day.
Drug interactions
The use of cefoperazone concurrently with certain drugs can lead to the development of the following effects:
- aminoglycosides: pharmaceutical incompatibility with cefoperazone. If necessary, combination therapy is used as a fractional sequential intravenous injection of an aminoglycoside and cefoperazone using two separate catheters;
- non-steroidal anti-inflammatory drugs (ibuprofen, diclofenac, ketorolac, indomethacin and others), thrombolytics, heparin, indirect anticoagulants and antiplatelet agents (alprostadil, courantil and others): increased risk of bleeding, hypoprothrombinemia;
- aminoglycosides, loop diuretics: increasing the likelihood of developing nephrotoxicity, especially in patients with renal failure;
- ethanol: incompatibility due to the likelihood of disulfiram-like reactions (hyperemia, nausea, vomiting, headache, shortness of breath, tachycardia, decreased blood pressure, abdominal cramps);
- drugs that reduce tubular secretion: an increase in the concentration of cefoperazone in the blood and a slowdown in its excretion.
Analogs
Analogs of Cefoperazone are: Dardum, Movoperiz, Medotsef, Operaz and others.
Terms and conditions of storage
Store in a dry, dark place at a temperature not exceeding 15 ° C.
Keep out of the reach of children.
Shelf life is 2 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Cefoperazone
In reviews of Cefoperazone, patients, as well as medical professionals, note that i / m injections of the drug often cause discomfort and unpleasant pain. It is reported that in such cases, the optimal choice for dissolving cephalosporin antibiotics is lidocaine, which in the required concentration provides effective dissolution of the drug and a powerful analgesic effect when administered intramuscularly.
Price for Cefoperazone in pharmacies
The price for Cefoperazone for 1 bottle of 1000 mg is approximately 107 rubles.
Anna Kozlova Medical journalist About the author
Education: Rostov State Medical University, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
